Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM).
TL;DR: In oestrogen receptor-positive, HER2-negative, lymph node-negative patients, multianalyte tests such as urokinase plasminogen activator (uPA)-PAI-1, Oncotype DX, MammaPrint, EndoPredict, Breast Cancer Index (BCI) and Prosigna (PAM50) may be used to predict outcome and aid adjunct therapy decision-making.
About: This article is published in European Journal of Cancer.The article was published on 2017-04-01 and is currently open access. It has received 356 citations till now. The article focuses on the topics: Oncotype DX & Breast cancer.
Citations
More filters
TL;DR: This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer as well as distinct risk profiles and treatment strategies.
Abstract: Importance Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250 000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer. Observations Breast cancer is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerlyHER2): hormone receptor positive/ERBB2 negative (70% of patients),ERBB2positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). More than 90% of breast cancers are not metastatic at the time of diagnosis. For people presenting without metastatic disease, therapeutic goals are tumor eradication and preventing recurrence. Triple-negative breast cancer is more likely to recur than the other 2 subtypes, with 85% 5-year breast cancer–specific survival for stage I triple-negative tumors vs 94% to 99% for hormone receptor positive andERBB2positive. Systemic therapy for nonmetastatic breast cancer is determined by subtype: patients with hormone receptor–positive tumors receive endocrine therapy, and a minority receive chemotherapy as well; patients withERBB2-positive tumors receiveERBB2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy; and patients with triple-negative tumors receive chemotherapy alone. Local therapy for all patients with nonmetastatic breast cancer consists of surgical resection, with consideration of postoperative radiation if lumpectomy is performed. Increasingly, some systemic therapy is delivered before surgery. Tailoring postoperative treatment based on preoperative treatment response is under investigation. Metastatic breast cancer is treated according to subtype, with goals of prolonging life and palliating symptoms. Median overall survival for metastatic triple-negative breast cancer is approximately 1 year vs approximately 5 years for the other 2 subtypes. Conclusions and Relevance Breast cancer consists of 3 major tumor subtypes categorized according to estrogen or progesterone receptor expression andERBB2gene amplification. The 3 subtypes have distinct risk profiles and treatment strategies. Optimal therapy for each patient depends on tumor subtype, anatomic cancer stage, and patient preferences.
2,310 citations
TL;DR: This work presents the results of a meta-analysis conducted at the 2016 European Oncology and Radiotherapy Guidelines Working Group (ESMO) workshop on breast cancer diagnosis and prognosis of women with atypical central giant cell granuloma (CGM) who have previously had surgery.
2,274 citations
TL;DR: Current research is focusing on tumor and circulating DNA and RNA and mutational status of ER (ESR1) for predicting the emergence of resistance to aromatase inhibitors and circulating tumor cells.
272 citations
Cites background or result from "Clinical use of biomarkers in breas..."
...Since the Oncotype DX test has been extensively validated, shown to reduce the use of adjuvant chemotherapy and to be cost-effective/cost saving, it is widely recommended for clinical use in Western countries [19]....
[...]
...Several of these tests are now recommended by expert panels (Table 3) [17-20] and are thus being increasingly used in clinical practice....
[...]
...Measurement of uPA and PAI-1 is now widely recommended for determining prognosis and therapy decision making, especially in lymph node-negative breast cancer patients [17,19]....
[...]
...However, in contrast to the EGTM guidelines [19], ASCO were opposed to the use of the RS in lymph node-positive patients....
[...]
...Patients at high risk based on clinical and pathological criteria but at low risk based on MammaPrint may be candidates for avoiding having to receive adjuvant chemotherapy” [19]....
[...]
TL;DR: Various imaging techniques and biochemical biomarkers could be utilized as diagnosis of patients with breast cancer and microRNAs and exosomes are highlighted as new diagnosis and therapeutic biomarkers for monitoring patients with Breast cancer.
Abstract: Breast cancer is a complex disease which is found as the second cause of cancer-associated death among women. Accumulating of evidence indicated that various factors (i.e., gentical and envirmental factors) could be associated with initiation and progression of breast cancer. Diagnosis of breast cancer patients in early stages is one of important aspects of breast cancer treatment. Among of various diagnosis platforms, imaging techniques are main diagnosis approaches which could provide valuable data on patients with breast cancer. It has been showed that various imaging techniques such as mammography, magnetic resonance imaging (MRI), positron-emission tomography (PET), Computed tomography (CT), and single-photon emission computed tomography (SPECT) could be used for diagnosis and monitoring patients with breast cancer in various stages. Beside, imaging techniques, utilization of biochemical biomarkers such as proteins, DNAs, mRNAs, and microRNAs could be employed as new diagnosis and therapeutic tools for patients with breast cancer. Here, we summarized various imaging techniques and biochemical biomarkers could be utilized as diagnosis of patients with breast cancer. Moreover, we highlighted microRNAs and exosomes as new diagnosis and therapeutic biomarkers for monitoring patients with breast cancer.
238 citations
Cites background or methods from "Clinical use of biomarkers in breas..."
..., miR-21, miR-10b, miR-155, and miR-145) could be used as diagnostic biomarkers for detection and monitoring breast cancer patients (Duffy et al., 2017; Kurozumi et al., 2017) (Table 2)....
[...]
...The suitable biomarkers could contribute to better understanding of cellular and molecular pathways involved in breast cancer pathogenesis (Duffy et al., 2017)....
[...]
...The employing of various biomarkers is known as one of important aspects of diagnosis and monitoring patients with breast cancer (Duffy et al., 2017)....
[...]
...The suitable biomarkers could contribute to better understanding of cellular and molecular pathways involved in breast cancer pathogenesis (Duffy et al., 2017)....
[...]
...…Her2, ER, and Ki67), mRNAs (i.e., ERα, ERβ, and ERRγ), enzymes (i.e., CEA and TSGF), and microRNAs (i.e., miR-21, miR-10b, miR-155, and miR-145) could be used as diagnostic biomarkers for detection and monitoring breast cancer patients (Duffy et al., 2017; Kurozumi et al., 2017) (Table 2)....
[...]
TL;DR: A within-patient comparison of the prognostic value of 6 multigene signatures in women with early ER-positive breast cancer who received endocrine therapy for 5 years found the ROR, BCI, and EPclin were significantly more prognostic for overall and late distant recurrence.
Abstract: IMPORTANCE Multiple molecular signatures are available for managing estrogen receptor (ER)-positive breast cancer but with little direct comparative information to guide the patient's choice. OBJECTIVE To conduct a within-patient comparison of the prognostic value of 6 multigene signatures in women with early ER -positive breast cancer who received endocrine therapy for 5 years. DESIGN, SETTING, AND PARTICIPANTS This retrospective biomarker analysis included 774 postmenopausal women with ER -positive ERBB2 (formerly HER2)-negative breast cancer. This analysis was performed as a preplanned secondary study of data from the Anastrozole or Tamoxifen Alone or Combined randomized clinical trial comparing 5-year treatment with anastrozole vs tamoxifen with 10-year follow-up data. The signatures included the Oncotype Dx recurrence score, PAM50-based Prosigna risk of recurrence (ROR), Breast Cancer Index (BCI), EndoPredict (EPclin), Clinical Treatment Score, and 4-marker immunohistochemical score. Data were collected from January 20 09, through April 2015. MAIN OUTCOMES AND MEASURES The primary objective was to compare the prognostic value of these signatures in addition to the Clinical Treatment Score (nodal status, tumor size, grade, age, and endocrine treatment) for distant recurrence for 0 to 10 years and 5 to 10 years after diagnosis. Likelihood ratio (LR) statistics were used with the chi(2) test and C indexes to assess the prognostic value of each signature. RESULTS In this study of 774 postmenopausal women with ER -positive, ERBB2-negative disease (mean [SD] age, 64.1[8] years), 591(mean [SD] age, 63.4 [7.9] years) had node -negative disease. The signatures providing the most prognostic information were the ROR (hazard ratio [HR], 2.56; 95% CI, 1.96-3.35), followed by the BCI (HR, 2.46; 95% CI, 1.88-3.23) and EPclin (HR, 2.14; 95% Cl, 171-2.68). Each provided significantly more information than the Clinical Treatment Score (HR, 1.99; 95% CI, 1.58-2.50), the recurrence score (HR, 1.69; 95% CI, 1.40-2.03), and the 4-marker immunohistochemical score (HR, 1.95; 95% CI, 1.55-2.45). Substantially less information was provided by all 6 molecular tests for the 183 patients with 1 to 3 positive nodes, but the BCI (Delta LR chi(2) = 9.2) and EPclin (Delta LR chi(2) = 7.4) provided more additional prognostic information than the other signatures. CONCLUSIONS AND RELEVANCE For women with node -negative disease, the ROR, BCI, and EPclin were significantly more prognostic for overall and late distant recurrence. For women with 1 to 3 positive nodes, limited independent information was available from any test. These data might help oncologists and patients to choose the most appropriate test when considering chemotherapy use and/or extended endocrine therapy.
225 citations
References
More filters
TL;DR: A system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts is developed, and a summary of the approach from the perspective of a guideline user is presented.
Abstract: Users of clinical practice guidelines and other recommendations need to know how much confidence they can place in the recommendations Systematic and explicit methods of making judgments can reduce errors and improve communication We have developed a system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts In this article we present a summary of our approach from the perspective of a guideline user Judgments about the strength of a recommendation require consideration of the balance between benefits and harms, the quality of the evidence, translation of the evidence into specific circumstances, and the certainty of the baseline risk It is also important to consider costs (resource utilisation) before making a recommendation Inconsistencies among systems for grading the quality of evidence and the strength of recommendations reduce their potential to facilitate critical appraisal and improve communication of these judgments Our system for guiding these complex judgments balances the need for simplicity with the need for full and transparent consideration of all important issues
7,608 citations
"Clinical use of biomarkers in breas..." refers background in this paper
...HER2 gene amplification or overexpression should be determined on all patients with primary invasive breast cancer (LOE, IA; SOR, A)....
[...]
...Oncotype DX: EGTM recommendation Oncotype DX RS may provide added value to established factors for determining prognosis and aiding decisionmaking with respect to administration of adjuvant chemotherapy in newly diagnosed breast cancer patients with lymph nodeenegative invasive disease that is ER-positive but HER2-negative (LOE, IB; SOR, A)....
[...]
...In agreement with previously published guidelines [1,3,21e24,36], the EGTM panel recommends that ER and PR be measured on all newly diagnosed primary invasive breast cancers (for ER, LOE IA; SOR, A and for PR, LOE 1B; SOR, A/B)....
[...]
...Patients at high risk based on clinical and pathological criteria but at low risk based on MammaPrint may be the candidates for avoiding having to receive adjuvant chemotherapy (LOE, IA; SOR,A)....
[...]
...In addition, Oncotype DX may be considered for identifying HER2negative, ER-positive patients with 1e3 involved lymph nodes for treatment with adjuvant chemotherapy (LOE, IB; SOR, A)....
[...]
TL;DR: The gene-expression profile studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.
Abstract: Background A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy. Methods Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node–negative disease, and 144 had lymph-node–positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. Results Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (±SE) overall 10-year survival rates were 54.6±4.4 percent and 94.5±2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6±4.5 percent in the group with a...
5,902 citations
TL;DR: The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer and could be used as a continuous function to predict distant recurrent in individual patients.
Abstract: background The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor–positive tumors is poorly defined by clinical and histopathological measures. methods We tested whether the results of a reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancerrelated genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. results Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan–Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. conclusions The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor–positive breast cancer.
5,685 citations
"Clinical use of biomarkers in breas..." refers background or methods in this paper
...low risk of recurrence (RS, <18; 51% of patients), intermediate risk of recurrence (RS, 18e31; 22% of patients) and high risk of recurrence (RS, >31; 27% of patients) [86]....
[...]
...The Oncotype DX test (Genomic Health Inc, Redwood City, CA, USA) involves measurement of the expression of 16 prognostic/predictive and five reference genes at the mRNA level by reverse transcriptase PCR in formalin-fixed and paraffin-embedded breast tumour tissue [86]....
[...]
TL;DR: A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed and strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored.
Abstract: Purpose To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker. Methods The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. Results Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. Recommendations The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly...
4,560 citations
University of Utah1, University of Michigan2, The Royal Marsden NHS Foundation Trust3, Ohio State University4, Indiana University5, St. Jude Medical Center6, University of Queensland7, Beaumont Hospital8, BC Cancer Agency9, University of Rochester10, Harvard University11, American Society of Clinical Oncology12, National Institutes of Health13, Baylor College of Medicine14, Sungkyunkwan University15, University of the West of England16, Tohoku University17, Radboud University Nijmegen18, University of Toronto19, Saint Joseph Mercy Health System20, Mayo Clinic21, University of Washington22, Memorial Hospital of South Bend23, University of Texas at Austin24, Johns Hopkins University25
TL;DR: An international Expert Panel that conducted a systematic review and evaluation of the literature and developed recommendations for optimal IHC ER/PgR testing performance recommended that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences.
Abstract: Purpose To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. Methods The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. Results Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria. Recommendations The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.
3,902 citations